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Article: DNA Damage Response Alterations in Ovarian Cancer: From Molecular Mechanisms to Therapeutic Opportunities.

Ovejero-Sánchez, María / González-Sarmiento, Rogelio / Herrero, Ana Belén

2023 Volume 15, Issue 2

Abstract: The DNA damage response (DDR), a set of signaling pathways for DNA damage detection and repair, maintains genomic stability when cells are exposed to endogenous or exogenous DNA-damaging agents. Alterations in these pathways are strongly associated with ... ...

Abstract	The DNA damage response (DDR), a set of signaling pathways for DNA damage detection and repair, maintains genomic stability when cells are exposed to endogenous or exogenous DNA-damaging agents. Alterations in these pathways are strongly associated with cancer development, including ovarian cancer (OC), the most lethal gynecologic malignancy. In OC, failures in the DDR have been related not only to the onset but also to progression and chemoresistance. It is known that approximately half of the most frequent subtype, high-grade serous carcinoma (HGSC), exhibit defects in DNA double-strand break (DSB) repair by homologous recombination (HR), and current evidence indicates that probably all HGSCs harbor a defect in at least one DDR pathway. These defects are not restricted to HGSCs; mutations in
Language	English
Publishing date	2023-01-10
Publishing country	Switzerland
Document type	Journal Article ; Review
ZDB-ID	2527080-1
ISSN	2072-6694
ISSN	2072-6694
DOI	10.3390/cancers15020448
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Article ; Online: Expanding the Spectrum of Skin Neoplasms in Muir-Torre Syndrome: Beyond Sebaceous Tumours.

Díaz-Calvillo, Pablo / Gómez-Jiménez, Carmen / Sabushimike, Doriane / González-Sarmiento, Rogelio / Roncero-Riesco, Mónica / Santos-Briz, Ángel

The American Journal of dermatopathology

2024 Volume 46, Issue 3, Page(s) 189–191

MeSH term(s)	Humans ; Muir-Torre Syndrome/genetics ; Muir-Torre Syndrome/pathology ; Sebaceous Gland Neoplasms/genetics ; Sebaceous Gland Neoplasms/pathology ; Skin Neoplasms/genetics ; Skin Neoplasms/pathology
Language	English
Publishing date	2024-02-14
Publishing country	United States
Document type	Journal Article
ZDB-ID	448469-1
ISSN	1533-0311 ; 0193-1091
ISSN (online)	1533-0311
ISSN	0193-1091
DOI	10.1097/DAD.0000000000002627
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Article ; Online: Synergistic effect of Chloroquine and Panobinostat in ovarian cancer through induction of DNA damage and inhibition of DNA repair.

Ovejero-Sánchez, María / González-Sarmiento, Rogelio / Herrero, Ana Belén

Neoplasia (New York, N.Y.)

2021 Volume 23, Issue 5, Page(s) 515–528

Abstract: Ovarian cancer (OC) is the deadliest gynecologic malignancy, which is mainly due to late-stage diagnosis and chemotherapy resistance. Therefore, new and more effective treatments are urgently needed. The in vitro effects of Panobinostat (LBH), a histone ... ...

Abstract	Ovarian cancer (OC) is the deadliest gynecologic malignancy, which is mainly due to late-stage diagnosis and chemotherapy resistance. Therefore, new and more effective treatments are urgently needed. The in vitro effects of Panobinostat (LBH), a histone deacetylase inhibitor that exerts pleiotropic antitumor effects but induces autophagy, in combination with Chloroquine (CQ), an autophagy inhibitor that avoid this cell survival mechanism, were evaluated in 4 OC cell lines. LBH and CQ inhibited ovarian cancer cell proliferation and induced apoptosis, and a strong synergistic effect was observed when combined. Deeping into their mechanisms of action we show that, in addition to autophagy modulation, treatment with CQ increased reactive oxygen species (ROS) causing DNA double strand breaks (DSBs), whereas LBH inhibited their repair by avoiding the correct recruitment of the recombinase Rad51 to DSBs. Interestingly, CQ-induced DSBs and cell death caused by CQ/LBH combination were largely abolished by the ROS scavenger N-Acetylcysteine, revealing the critical role of DSB generation in CQ/LBH-induced lethality. This role was also manifested by the synergy found when we combined CQ with Mirin, a well-known homologous recombination repair inhibitor. Altogether, our results provide a rationale for the clinical investigation of CQ/LBH combination in ovarian cancer.
MeSH term(s)	Antineoplastic Agents/pharmacology ; Apoptosis/drug effects ; Autophagy/drug effects ; Cell Cycle Checkpoints/drug effects ; Cell Cycle Checkpoints/genetics ; Cell Line, Tumor ; Cell Survival/drug effects ; Chloroquine/pharmacology ; DNA Breaks, Double-Stranded/drug effects ; DNA Damage/drug effects ; DNA Repair/drug effects ; Drug Synergism ; Female ; Humans ; Ovarian Neoplasms/genetics ; Ovarian Neoplasms/metabolism ; Ovarian Neoplasms/pathology ; Panobinostat/pharmacology ; Reactive Oxygen Species/metabolism ; Recombinational DNA Repair
Chemical Substances	Antineoplastic Agents ; Reactive Oxygen Species ; Chloroquine (886U3H6UFF) ; Panobinostat (9647FM7Y3Z)
Language	English
Publishing date	2021-04-27
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	1483840-0
ISSN	1476-5586 ; 1522-8002
ISSN (online)	1476-5586
ISSN	1522-8002
DOI	10.1016/j.neo.2021.04.003
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Article: Commentary: Genomic Analysis Reveals Heterogeneity Between Lesions in Synchronous Primary Right-Sided and Left-Sided Colon Cancer.

Perea, José / Corchete, Luis / García, Juan L / Urioste, Miguel / González-Sarmiento, Rogelio

Frontiers in molecular biosciences

2022 Volume 8, Page(s) 803707

Language	English
Publishing date	2022-01-21
Publishing country	Switzerland
Document type	Journal Article ; Comment
ZDB-ID	2814330-9
ISSN	2296-889X
ISSN	2296-889X
DOI	10.3389/fmolb.2021.803707
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Article ; Online: Analysis of endothelial gene polymorphisms in Spanish patients with vascular dementia and Alzheimer´s disease.

Manso-Calderón, Raquel / Cacabelos-Pérez, Purificación / Sevillano-García, M Dolores / Herrero-Prieto, M Elisa / González-Sarmiento, Rogelio

Scientific reports

2023 Volume 13, Issue 1, Page(s) 13441

Abstract: There is increasing evidence for the involvement of blood-brain barrier (BBB) in vascular dementia (VaD) and Alzheimer´s disease (AD) pathogenesis. However, the role of endothelial function-related genes in these disorders remains unclear. We evaluated ... ...

Abstract	There is increasing evidence for the involvement of blood-brain barrier (BBB) in vascular dementia (VaD) and Alzheimer´s disease (AD) pathogenesis. However, the role of endothelial function-related genes in these disorders remains unclear. We evaluated the association of four single-nucleotide polymorphisms (VEGF, VEGFR2 and NOS3) with diagnosis and rate of cognitive decline in AD and VaD in a Spanish case-control cohort (150 VaD, 147 AD and 150 controls). Participants carrying -604AA genotype in VEGFR2 (rs2071559) were less susceptible to VaD after multiple testing. Further analysis for VaD subtype revealed a significant difference between small-vessel VaD patients and controls, but not for large-vessel VaD patients. In addition, -2578A and -460C alleles in VEGF (rs699947 and rs833061) showed to decrease the risk of AD, whereas NOS3 (rs1799983) influenced disease progression. Our study supports previous findings of a deleterious effect of VEGFR2 reduced expression on small-vessel disease, but not on large-vessel disease; as well as a detrimental effect of down-regulating VEGF and eNOS in AD, affecting vascular permeability and neuronal survival. These data highlight the relevance of endothelial function and, therefore, BBB in both VaD and AD.
MeSH term(s)	Humans ; Alzheimer Disease/genetics ; Dementia, Vascular/genetics ; Vascular Endothelial Growth Factor A/genetics ; Polymorphism, Single Nucleotide ; Alleles
Chemical Substances	Vascular Endothelial Growth Factor A
Language	English
Publishing date	2023-08-18
Publishing country	England
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	2615211-3
ISSN	2045-2322 ; 2045-2322
ISSN (online)	2045-2322
ISSN	2045-2322
DOI	10.1038/s41598-023-39576-7
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Article ; Online: Endothelial nitric oxide synthase rs1799983 gene polymorphism is associated with the risk of developing intracranial aneurysm.

Usategui-Martín, Ricardo / Jiménez-Arribas, Paloma / Sakas-Gandullo, Carmen / González-Sarmiento, Rogelio / Rodríguez-Arias, Carlos A

Acta neurochirurgica

2023 Volume 165, Issue 5, Page(s) 1261–1267

Abstract: Purpose: The intracranial aneurysm (IA) rupture is associated with a subarachnoid hemorrhage. One third of patients die, and one third remain depend for daily activities. Genetic factors are crucial in the formation and clinical evolution of IAs. ... ...

Abstract	Purpose: The intracranial aneurysm (IA) rupture is associated with a subarachnoid hemorrhage. One third of patients die, and one third remain depend for daily activities. Genetic factors are crucial in the formation and clinical evolution of IAs. Multiple loci have been associated with AIs, much of them implicating multiple pathways related to vascular endothelial maintenance and extracellular matrix integrity. Thus, the aim of our study was to characterize whether polymorphisms in genes implicated in the vascular endothelial maintenance could modify the risk of developing IAs. Subjects and methods: We have studied 176 patients with IA recruited in the Service of Neurosurgery at the University Hospital of Valladolid (Spain) and a control group if 150 sex-matched healthy subjects. Clinical variables were collected from each patient. We have analyzed VEGFA rs833061, VEGFR2 rs2071559, endothelin rs5370, endoglin rs3739817, and eNOS rs1799983 polymorphisms. Results: Our results showed that allele T of the eNOS rs1799983 polymorphism is correlated with decreased risk of developing the disease; thus, allele G of the eNOS rs1799983 polymorphism increased the risk of developing IA. Conclusion: The association of eNOS rs1799983 polymorphism with the risk to suffer IA reinforces the hypothesis that genetic variants in eNOS gene could be crucial in the pathogenesis of IA.
MeSH term(s)	Humans ; Intracranial Aneurysm/genetics ; Intracranial Aneurysm/complications ; Nitric Oxide Synthase Type III/genetics ; Polymorphism, Genetic ; Subarachnoid Hemorrhage/complications ; Aneurysm, Ruptured/genetics ; Aneurysm, Ruptured/complications ; Polymorphism, Single Nucleotide/genetics ; Genetic Predisposition to Disease/genetics ; Case-Control Studies
Chemical Substances	Nitric Oxide Synthase Type III (EC 1.14.13.39)
Language	English
Publishing date	2023-03-18
Publishing country	Austria
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	80010-7
ISSN	0942-0940 ; 0001-6268
ISSN (online)	0942-0940
ISSN	0001-6268
DOI	10.1007/s00701-023-05552-3
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Article ; Online: Ichthyosis.

Gutiérrez-Cerrajero, Carlos / Sprecher, Eli / Paller, Amy S / Akiyama, Masashi / Mazereeuw-Hautier, Juliette / Hernández-Martín, Angela / González-Sarmiento, Rogelio

Nature reviews. Disease primers

2023 Volume 9, Issue 1, Page(s) 2

Abstract: The ichthyoses are a large, heterogeneous group of skin cornification disorders. They can be inherited or acquired, and result in defective keratinocyte differentiation and abnormal epidermal barrier formation. The resultant skin barrier dysfunction ... ...

Abstract	The ichthyoses are a large, heterogeneous group of skin cornification disorders. They can be inherited or acquired, and result in defective keratinocyte differentiation and abnormal epidermal barrier formation. The resultant skin barrier dysfunction leads to increased transepidermal water loss and inflammation. Disordered cornification is clinically characterized by skin scaling with various degrees of thickening, desquamation (peeling) and erythema (redness). Regardless of the type of ichthyosis, many patients suffer from itching, recurrent infections, sweating impairment (hypohidrosis) with heat intolerance, and diverse ocular, hearing and nutritional complications that should be monitored periodically. The characteristic clinical features are considered to be a homeostatic attempt to repair the skin barrier, but heterogeneous clinical presentation and imperfect phenotype-genotype correlation hinder diagnosis. An accurate molecular diagnosis is, however, crucial for predicting prognosis and providing appropriate genetic counselling. Most ichthyoses severely affect patient quality of life and, in severe forms, may cause considerable disability and even death. So far, treatment provides only symptomatic relief. It is lifelong, expensive, time-consuming, and often provides disappointing results. A better understanding of the molecular mechanisms that underlie these conditions is essential for designing pathogenesis-driven and patient-tailored innovative therapeutic solutions.
MeSH term(s)	Humans ; Quality of Life ; Ichthyosis/diagnosis ; Ichthyosis/genetics ; Eye ; Genetic Association Studies
Language	English
Publishing date	2023-01-19
Publishing country	England
Document type	Journal Article ; Review
ISSN	2056-676X
ISSN (online)	2056-676X
DOI	10.1038/s41572-022-00412-3
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Article: Oral Rehabilitation as Part of a Multidisciplinary Treatment in a Case Study of Pigmentary Incontinence.

Cano-Rosás, Mónica / Vicente-Jiménez, Joaquín de / Diosdado-Cano, José María / Suárez-Quintanilla, David / González-Sarmiento, Rogelio / Curto, Daniel / Curto, Adrián

Children (Basel, Switzerland)

2023 Volume 10, Issue 9

Abstract: We present the clinical course of a 9-year-old female patient with Bloch-Sulzberger syndrome and severe neurological deficit that met the major (classic cutaneous signs) and minor (dental anomalies and retinal pathology) diagnostic criteria of Landy and ... ...

Abstract	We present the clinical course of a 9-year-old female patient with Bloch-Sulzberger syndrome and severe neurological deficit that met the major (classic cutaneous signs) and minor (dental anomalies and retinal pathology) diagnostic criteria of Landy and Donnai. Longitudinal multidisciplinary follow-up was carried out from birth to adulthood. Neurological involvement was assessed with electroencephalographic (EEG) and neuroimaging tests at different times during the patient's life. Cranio-maxillofacial involvement was evaluated using lateral skeletal facial and cephalometric analyses. The right and left facial widths were measured through frontal face analysis and using the vertical zygomatic-midline distance. Oral rehabilitation was performed through orthodontic treatment and major dental reconstruction using composite resins. This treatment aimed to improve the occlusion and masticatory function, relieve the transversal compression of the maxilla, and reconstruct the fractured teeth. We believe that, due to significant neurological and cognitive impairment, orthognathic surgery was not the best option for restoring function and improving oral health-related quality of life.
Language	English
Publishing date	2023-09-04
Publishing country	Switzerland
Document type	Case Reports
ZDB-ID	2732685-8
ISSN	2227-9067
ISSN	2227-9067
DOI	10.3390/children10091505
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Article ; Online: Effects of Physical Exercise on Telomere Length in Healthy Adults: Systematic Review, Meta-Analysis, and Meta-Regression.

Sánchez-González, Juan Luis / Sánchez-Rodríguez, Juan Luis / Varela-Rodríguez, Sergio / González-Sarmiento, Rogelio / Rivera-Picón, Cristina / Juárez-Vela, Raúl / Tejada-Garrido, Clara Isabel / Martín-Vallejo, Javier / Navarro-López, Víctor

JMIR public health and surveillance

2024 Volume 10, Page(s) e46019

Abstract: Background: Physical exercise is one of the main nonpharmacological treatments for most pathologies. In addition, physical exercise is beneficial in the prevention of various diseases. The impact of physical exercise has been widely studied; however, ... ...

Abstract	Background: Physical exercise is one of the main nonpharmacological treatments for most pathologies. In addition, physical exercise is beneficial in the prevention of various diseases. The impact of physical exercise has been widely studied; however, existing meta-analyses have included diverse and heterogeneous samples. Therefore, to our knowledge, this is the first meta-analysis to evaluate the impact of different physical exercise modalities on telomere length in healthy populations. Objective: In this review, we aimed to determine the effect of physical exercise on telomere length in a healthy population through a meta-analysis of randomized controlled trials. Methods: A systematic review with meta-analysis and meta-regression of the published literature on the impact of physical exercise on telomere length in a healthy population was performed. PubMed, Cochrane Library, SCOPUS, Web of Science, and Embase databases were searched for eligible studies. Methodological quality was evaluated using the Risk Of Bias In Nonrandomized Studies of Interventions and the risk-of-bias tool for randomized trials. Finally, the certainty of our findings (closeness of the estimated effect to the true effect) was evaluated using Grading of Recommendations, Assessment, Development, and Evaluations (GRADE). Results: We included 9 trials that met the inclusion criteria with fair methodological quality. Random-effects model analysis was used to quantify the difference in telomere length between the exercise and sham groups. Meta-analysis showed that exercise did not significantly increase telomere length compared with the control intervention (mean difference=0.0058, 95% CI -0.05 to 0.06; P=.83). Subgroup analysis suggested that high-intensity interventional exercise significantly increased telomere length compared with the control intervention in healthy individuals (mean difference=0.15, 95% CI 0.03-0.26; P=.01). Furthermore, 56% of the studies had a high risk of bias. Certainty was graded from low to very low for most of the outcomes. Conclusions: The findings of this systematic review and meta-analysis suggest that high-intensity interval training seems to have a positive effect on telomere length compared with other types of exercise such as resistance training or aerobic exercise in a healthy population. Trial registration: PROSPERO CRD42022364518; http://tinyurl.com/4fwb85ff.
MeSH term(s)	Adult ; Humans ; Databases, Factual ; Exercise ; Health Status ; Telomere ; Telomere Homeostasis
Language	English
Publishing date	2024-01-09
Publishing country	Canada
Document type	Journal Article ; Meta-Analysis ; Systematic Review
ISSN	2369-2960
ISSN (online)	2369-2960
DOI	10.2196/46019
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Article ; Online: Corrigendum.

Blanco-Antona, Francisco / González-Sarmiento, Rogelio / García-Cenador, Begoña / Lozano, Francisco S

Pain medicine (Malden, Mass.)

2021 Volume 23, Issue 1, Page(s) 226

Language	English
Publishing date	2021-09-04
Publishing country	England
Document type	Published Erratum
ZDB-ID	2015903-1
ISSN	1526-4637 ; 1526-2375
ISSN (online)	1526-4637
ISSN	1526-2375
DOI	10.1093/pm/pnab186
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